The biodiversity observed on the planet earth provides vast varieties of plants/trees which are explored over the centuries to understand their use in daily life both as source of food and medicine. The use of plants as a source of medicine came to limelight with Ayurveda which was developed between 2500 and 500 BC in India. India, a land known for tradition and herbal resource, recorded around 20,000 medicinal plants out of which only 35-40% are explored by the traditional communities.
Medicinal plants like Aswagandha, Amla, Brahmi, Guggul, Long pepper, Tulsi, Henna, Haridra, Neem and many more have been traditionally in use for treating various ailments via Ayurveda, Siddha, Unani and other traditional methods. The traditional medicinal system used these rich herbal sources either alone or in combination, together with other required ingredients to treat various conditions. Despite these uses of medicinal plants over the years there has been a lag to deliver a therapeutically efficacious drug/nutraceutical from a plant source. The traditional system of medicine had little scientific effort to validate these anecdotal uses that are traditionally known.
Despite the long historical use, little has been achieved in treating the diseases. The major problem associated with hydrophobic plant compounds and extracts is their poor bioavailability, leading to poor or decreased efficacy. The major hydrophobic compounds with poor bioavailability in plant extracts belong to phenolic compounds, flavonoids, stilbenes and lignans. Flavoniods may themselves be divided into 6 subclasses based on the type of heterocycle involved: flavonols, flavones, isoflavones, flavanones, anthocyanidins, and flavanols (catechins and proanthocyanidins). Most of the hydrophobic compounds like Curcuminoids, Boswellic acids, Resveratrol, Hypericin, Bacosides, Xanthorhizol, Ginseng extract, Gingko biloba extract and many others are proven to have several therapeutic benefits like anti-inflammatory, anti-oxidant, anti-obese, memory enhancing, anti-allergic, anti-microbial, anti-cancerous and many other medicinal activities. But, little has been achieved with respect to these molecules for the prevention and treatment of diseases due to their poor bioavailability and lack of sustained release in the body.
Many of the plant molecules as discussed above are hydrophobic in nature and hence are not water soluble. The poor bioavailability of these molecules reflects the lack of efficient natural drugs in the market, in spite of their traditionally known benefits. On the other hand, biopharmaceuticals have been suffering from instability and biological degradation before reaching the target site.
One of the best and thoroughly studied molecule that can be exemplified here is Curcumin. Curcumin and derivatives like Bisdemethoxycurcumin, Demethoxycurcumin, Bis-o-demethylcurcumin have been widely acknowledged as a botanical supplement with great potential to prevent and treat wide spectrum of therapeutic conditions. In addition, they have been proved to be remarkably safe in animal studies and in many clinical evaluations even at high doses (up to 12 g/day). However, the major problem limiting the commercial exploitation of their therapeutic effects is their low bioavailability and their fast elimination from the body, very often as quickly as in 30 mins.
The reasons for the poor bioavailability of curcuminoids may be attributed to poor absorption, high rate of metabolism and/or rapid elimination and clearance from the body. This is the same case with any of the hydrophobic plant molecules/extracts. Several studies failed to detect these compounds in the blood plasma/serum even after administration of high doses in animals and humans. Most of the phytochemicals such as curcumin and resveratrol show bioavailability of less than 1%. Curcumin when taken orally get metabolized to form curcumin glucoronide, curcumin sulphate, which are not biologically active and thus are eliminated from the system, which in turns leads to poor efficacy.
Many of the existing curcumin products in market are unformulated turmeric extract or formulated with suitable excipients to enhance the bioavailability. Some curcumin products use Phospholipids to enhance the bioavailability of curcumin. Other curcumin formulations contain piperine to enhance curcumin bioavailability.
The main issue to be addressed with the hydrophobic compounds is not only the bioavailability but also their availability in the systemic circulation for longer period (24 hours or more) in an biologically active form for sustained efficacy. An ideal formulation would be the one which can be retained in the body over a period of 12-24 hours and more, with significant amount of the active compound in the blood stream to provide the required therapeutic benefits. This could minimize the expenditure due to reduced dose and patient compliance of convenient dosing.
The time to reach maximum concentration (Tmax), Maximum concentration (Cmax), Area under the curve (AUC) and Half-life (T1/2) are some of the important parameters to establish the systemic bioavailability of a particular drug/formulation. For a drug intended to provide sustained release and enhanced bioavailability, AUC should be higher with higher value for t½. Higher t½ indicates the longer stay of drug in the body and hence long lasting efficacy.
The product of above features will reduce the dose levels and also achieves enhanced bioavailability leading to enhanced therapeutic efficacy compared to existing products in market. The currently available phyto pharmaceutical compositions are way behind in providing a highly bioavailable and sustained release formulation, which is stable and water soluble.
Moreover the conventional methods and regular solubilization techniques are not efficient enough to solubilize high concentration of the plant molecules/extracts and also not successful in providing sustained release. Due to their lipophilic and hydrophobic nature, the choice of the right excipients, right combination of excipients and process of formulating such product is key to achieve the desired product.
Emulsifiers, which are classified under surfactants and also lipids, are widely used for solubilizing hydrophobic compounds and in formulating nanoemulsions.
Currently many curcuminoid products in market claim high bioavailability which are formulated using phospholipids or plant derived oils and so on. However, none of the prior arts discloses a nanoformulation containing unique proportion of the plant derived hydrophobic active compound(s) in an emulsifier phase and aqueous phase to achieve sustained release over a 24 hr time period and more.
Further, none of the prior art discloses the use of aqueous phase in combination with emulsifier phase to achieve a nanoemulsion with smaller particle size for sustained release and enhanced efficacy.
Hence, the present disclosure provides a unique proportion of the plant derived hydrophobic active compound(s) in an emulsifier phase and aqueous phase to provide enhanced efficacy and sustained release over a 24 hr time period and more.
Accordingly the present disclosure offers a potential successor in the field of drugs, biopharmaceuticals, nutritional/dietary supplements for human and/or animal application with a novel nanoemulsified composition with enhanced bioavailability and sustained release.